Pharmacovigilance is the science and activities
relating to the detection, assessment, understanding and prevention of
adverse effects or any other possible drug-related problems(1). An
"adverse event" is defined as any untoward medical occurrence that may
present during treatment with a drug but which does not necessarily
have a causal relationship with its use(1). An "adverse drug reaction"
is any noxious, unintended and undesired effect of a drug, which
occurs at a dose used in humans for prophylaxis, diagnosis, therapy or
modification of physiological functions(2). Spontaneous reporting of
adverse events and adverse drug reactions is the commonest method
utilized for generating safety data(3).

Adverse drug reactions in children constitute a
significant health issue given their reported incidence of 9.5%. They
also account for 2.1% of hospital admissions, with 39.3% of them being
life-threatening(1,4). Safety data generated from clinical trials is
incapable of identifying infrequent or late-onset adverse drug
reactions(5). When a new drug is marketed, only limited information
regarding its safety in children is available. Currently, several new
drugs are being launched in India almost simultaneously as in the
world market. Hence even minimal post-marketing safety data is
unavailable(6). The types of diseases and co-morbid conditions (e.g.,
malnutrition, anemia and infestations) in Indian children, diverse
genetic composition, and concomitant use of drugs belonging to
alternative medicine could result in unforeseeable adverse drug
reactions(7-9). Hence, it is mandatory that our country should have an
active pharmacovigilance network.

Pharmacovigilance benefits everybody: The patients
are protected from unsafe drugs; doctors and pharmaceutical industry
keep their reputations intact and drug regulators receive pertinent
data that helps them to take regulatory decisions. Although, Indian
Council of Medical Research and Drugs Controller General of India
began establishing Adverse Drug Reaction centers in 1980s, these
activities remained confined to a few institutions and practicing
doctors have remained largely oblivious of these activities(7,10).

National Pharmacovigilance Program

To improve the current state of functioning of
pharmacovigilance activities, the central drug regulatory agency. The
Central Drugs Standard Control Organization launched the National
Pharmacovigilance Program in November 2004 under the aegis of
Directorate General of Health Services, Union Ministry of Health and
Family Welfare. The basic purpose of this program is to collate,
analyze and archive adverse drug reaction data for making regulatory
decisions regarding drugs marketed in India. The program has a
three-tier structure consisting of peripheral, regional and zonal
Pharmacovigilance Centers in addition to the National
Pharmacovigilance Advisory Committee and the National
Pharmacovigilance Center based at the Central Drugs Standard Control
Organization, New Delhi at its apex (Fig. 1). All centers can
report alarming or critical adverse drug reactions to the National
Pharmacovigilance Center directly so that regulatory decisions can be
taken promptly.

Fig. 1. National Pharmacovigilance Program: Selected
Functions Carried Out at Various Levels.

National Pharmacovigilance Center (NPC) at the
CDSCO, New Delhi

 To monitor ADRs to medicines

 To review PSURs submitted by the
pharmaceutical companies

 To provide recommendations to the CDSCO
regarding regulatory matters such as product label amendments,
product suspension and product withdrawal

 To liaise with international regulatory
bodies working in the fields of phramacovigilance

 To conduct special pharmacovigilance projects on drugs
of special concern to the NPP

Five Regional Pharmacovigilance Centers (RPC)

 To act as a PPC and generate its own AE
data

 To collate and scrutinize the data
obtained from the PPC under its umbrella

 To perform causality assessment on AE
reported

 To transmit its data to ZPC on a
fortnightly basis

 To transmit critical and alarming ADR
data to NPC directly to enable it to take prompt regulatory
actions and to transmit all serious ADR data to ZPC within two
working days

 To audit its functioning

 To identify, induce PPC, provide them
technical support and supervise over and coordinate the
functioning of PPC under its umbrella

 To liaise with healthcare professionals
and organize training programs and interactive meetings

 To undertake performance audit and implement corrective
measures

Peripheral Pharmacovigilance Centers (PPC)

 To record and forward ADR forms and
other relevant information on a weekly basis to the RPC

 To transmit all serious AE to NPC
within two working days

 To liaise with healthcare professionals
and train its staff through training programs and interactive
meetings

 To undertake performance audit and implement corrective
measures

Under the program, Peripheral Pharmacovigilance
Centers will be established in teaching and non-teaching hospitals,
clinics and pharmacies in each state and union territory. Each
Peripheral Pharmacovigilance Center will record adverse events and
forward the adverse drug reaction forms and relevant information to
its respective Regional Pharmacovigilance Center on a weekly basis.
The Regional Pharmacovigilance Centers would cover five regions of the
country: North, East, Central, West, and South and will be responsible
for recording adverse drug reaction data locally and scrutinizing data
received from the Peripheral Pharmacovigilance Centers situated in
their respective regions. Each Regional Pharmacovigilance Center will
subject its data to causality assessment and also report to its Zonal
Pharmacovigilance Center. Two Zonal Pharmacovigilance Centers have
been established: at KEM Hospital, Mumbai and at All India Institute
of Medical Sciences, New Delhi. In addition to generating its own
adverse drug reaction data and performing causality assessment, each
Zonal Pharmacovigilance Center would also prepare reports for the
National Pharmacovigilance Center and conduct special
pharmacovigilance projects on any drug of special concern to the
National Pharmacovigilance Programme. The National Pharmacovigilance
Center would recommend the Central Drugs Standard Control Organization
regarding regulatory actions (including amendments to label and
suspension or withdrawal of the product) based on the adverse drug
reaction data generated in the country and Periodic Safety Update
Reports submitted by pharmaceutical companies. It would disseminate
relevant information through adverse drug reaction news bulletins,
drug alerts and seminars. As a part of international collaboration,
the National Pharmacovigilance Center will network with national
pharmacovigilance bodies from other countries and also provide data
for the World Health Organization International Drug Monitoring
program.

Noteworthy Features of NPP

 Its immediate objective is to foster a culture
of notification not only amongst doctors but also amongst other
healthcare providers, viz., pharmacists and nurses.

 Although the drug regulators would be more
interested in receiving information on adverse drug reactions of
newly marketed drugs, the program allows reporting of common or
non-serious adverse drug reactions of even well established drugs.
This has been done to encourage every healthcare provider to start
reporting adverse events.

 The reporting forms maintain patient
confidentiality. Identification of notifier, however, is obligatory
to allow for verification of information and discourage submission
of spurious data.

 Now even practicing doctors and pharmacists can
establish Peripheral Pharmacovigilance Centers and get involved in
pharmacovigilance. Earlier only pharmacologists were involved.

Considerations for the Future

The program represents a significant commitment to
help generate adverse drug reaction data. Various stakeholders can
help the program achieve its objectives comprehensively:

For Program Managers

 Involve professional organizations of
healthcare providers (e.g., Indian Academy of Pediatrics,
National Neonatology Forum, Indian Medical Association, Association
of Physicians of India, Trained Nurses Association of India, Indian
Pharmaceutical Association, Indian Hospital Pharmacists
Association) to educate their members about the program and there by
sustain their participation.

 Use of other modes of communication: In
addition to the Central Drugs Standard Control Organization website,
use news-letters and pamphlets to inform healthcare providers about
the programs activities.

 Address clinicians concerns: Doctors
may be hesitant to report adverse events on medico-legal grounds and
fear of public outcry. They will feel secure if steps are taken to
inform the public that an unexpected adverse event occurring during
therapy need not necessarily be drug-related, even though it may
have to be reported as an adverse event.

 Focus on drug safety issues in children:
At present, the National Pharmacovigilance Advisory Committee does
not have a pediatrician as its member. It should co-opt at least one
expert Indian Academy of Pediatrics-recommended pediatrician on its
panel.

 Collect adverse drug reaction data involving
drugs of alternative medicine and their interactions with drugs of
modern medicine.

 Consider including reports of "lack of
efficacy" and poisoning.

 Establish a link with public healthcare
authorities to obtain data regarding adverse events following
immunization.

 Make the Central Drugs Standard Control
Organization website more informative by providing the latest data
about the adverse events/ adverse drug reactions reported, their
causal relationship and performance reports. The program newsletters
should be available at the website.

 Recognize the contribution of notifiers and
centers with consistent high quality performance through citation on
the website and in the newsletter to help motivate everyone to
report adverse events.

 Allow healthcare providers working in rural
areas and at primary health centers to avail Internet and facsimile
facilities to report adverse events: This would encourage reporting
from remote areas, help expand the programs coverage and cut the
red tape.

For Pharmacovigilance Centers

 Each center should set up an institutional
pharmacovigilance committee to sustain this program. It should
present its adverse drug reaction data at institutional meetings and
disseminate information regarding unusual adverse drug reactions
through institutional newsletter or website to help engage its
healthcare providers.

 Act locally: Each center should
establish rapport with all the doctors and pharmacists in its
locality and satisfy their "felt needs" about drug information, new
formulations and management of adverse events, when encountered.

 Local networking: Without waiting for
the linkages at central level to percolate downward, each center
should network with local branches of professional organizations to
reach their members.

 Extend more than common courtesies:
Provide information about similar reports, feedback of the causality
assessment and enlist the notifier as a partner when the adverse
drug reaction is presented or published.

 The Academy has shown its commitment to ensure
safe use of drugs in children by establishing a pharmacology cell,
having its own adverse drug reaction reporting form and publishing
an Indian Academy of Pediatrics drug formulary. Being an important
stakeholder, the Indian Academy of Pediatrics should also take the
initiative in collaborating with the program managers by
sensitizing, informing and educating its members about the National
Pharmacovigilance Program by regularly allotting time for discussion
on pharmacovigilance at the various academic events organized by its
branches all over the country.

 Its official journal, Indian Pediatrics, should
have a regular column related to drug safety in children and
encourage publication of pediatric adverse drug reaction data.

Pediatricians should appreciate that now there is a
system and a tool in place to collect and analyze adverse drug
reaction data. They should start reporting adverse events and actively
participate in the National Pharmacovigilance Program to help ensure
that children in our country receive safe drugs.

Acknowledgements

The authors wish to thank Dr. Nilima A. Kshirsagar,
Dean, Seth GS Medical College and KEM Hospital, Mumbai for permitting
them to publish this article

Contributors: SBB was responsible for the
concept, drafting of the manuscript, final approval of the version and
will act as the guarantor of the article. SK was responsible for
discussing core ideas, critical revision of the manuscript for
intellectual content and final approval of the version.

Competing interests: SBB participated in the
meeting held in Mumbai in March 2003 to evolve consensual protocol for
the National Pharmacovigilance Program. SK is a member of the Adverse
Event Monitoring Cell at his institution.

Funding: None.

Key Messages

 The National
Pharmacovigilance Program has been launched to improve the
current state of functioning of pharmacovigilance activities.
Its basic purpose is to analyze adverse drug reaction data for
making regulatory decisions regarding drugs marketed in India.

 Not only doctors but other healthcare
providers, viz., pharmacists and nurses can now actively
participate in the program. They should start reporting adverse
events to help ensure that children in our country receive safe
drugs.